Aggression has become an increasingly popular topic of interest within the field of psychology. What leads to aggressive behavior? Are people born with aggressive tendencies? Is it a combination of genetic and environmental factors?
Brunner et al. (1993) was one of the first to discover a genetic basis for violent, aggressive behaviors. Based on a case study of a Dutch family with a vast history of violent males, he found an irregularity in the monoamine oxidase A (MAOA) gene, located in the X chromosome. Additionally, analysis of 24-hour urine samples indicated a deficiency in monoamine metabolism, which suggested a lack of degradation of monoamine neurotransmitters. Collectively, Brunner et al. realized the MAOA gene was not only potentially associated with the abnormal behavior of these males but was an indirect mediator of them; the gene seemed to be far more complex in its ability to dysregulate neurochemicals.
Currently, scientists now know that the MAOA gene produces the monoamine oxidase A enzyme, which is primarily responsible for the active degradation of monoamine neurotransmitters, such as serotonin (5-HT), to help prevent neurotransmitter accumulation within the brain (U.S. National Library of Medicine, 2020). Specifically, after the presynaptic cleft releases neurotransmitters to bind to receptors in the postsynaptic cleft, known as the target cell, the neurotransmitters are typically removed actively, such as through enzymatic degradation. This involves catabolizing the neurotransmitter within the synapse until it is no longer recognized by the receptors of the target cell (Jensen).
However, the MAOA-L allele produces a low-activity version of this enzyme, meaning serotonin will not be properly degraded. This results in an accumulation of this neurotransmitter in the brain, which appears to be a contributory factor to aggression. (U.S. National Library of Medicine, 2020).
The same effects between the MAOA-L allele, serotonergic accumulation, and aggressive behavior can be observed in mice, as demonstrated by Cases et al. (1995). The study compared aggression and impulsivity in Tg8 mice that had a deletion in MAOA exons 2 and 3, which developed the MAOA-L allele, while C3H mice had no MAOA deficiencies. One of their investigations involved a resident-intruder test, in which each mouse was placed in their typical cage with a two-month-old intruding mouse for ten minutes. The C3H mice appeared to investigate the cage, while Tg8 mice showed a “static, hunched, fluffed-fur posture” (p. 1764). Additionally, when the intruder was found, the Tg8 mice attacked the intruder faster than the C3H mice, suggesting impulsive, aggressive behavior. When later comparing the amount of serotonin in Tg8 and C3H brains, Cases et al. (1995) found that Tg8 mice showed extreme increases in serotonin compared to the C3H mice.
Interestingly, evidence of the effect of the MAOA-L allele in aggressive behavior can even be seen through brain activity and brain plasticity. Meyer-Lindenberg et al. (2006), for instance, conducted a study whereby MAOA-L and MAOA-H predisposed participants were exposed to images of neutral, fearful, and angry facial expressions under an fMRI. The results showed that when MAOA-L individuals viewed angry and fearful faces, they showed significant activation in the amygdala compared to individuals with the MAOA-H allele—one that predisposes high activity MAOA enzymes—viewed said facial expressions. Since the amygdala is a part of the brain associated with emotional response and impulsive reactivity, a high activation from this part of the brain suggests that threatening stimuli results in more impulsive, aggressive reactions in those with MAOA-L (Amaral, 2003). Thus, the correlation between the MAOA-L allele and the amygdala suggests the role of MAOA in aggressive behavior.
That said, there appears to be a perplexing relationship between the accumulation of serotonin and aggressive behavior. Serotonin is a neurotransmitter typically associated with prosocial behavior (Seigal & Crockett, 2013). Thus, intuitively, more serotonin in the brain would likely produce more prosocial effects. However, this contradiction was resolved by another brain analysis by Meyer-Lindenberg et al., which demonstrates the concept of down-regulation as the potential explanation. Downregulation is the process by which postsynaptic receptors shut off to prevent over-stimulating the brain with a particular neurotransmitter (U.S. National Library of Medicine, 2020). This aims to prevent excessive amounts of neurotransmitter from being transmitted throughout the brain. Further support for the explanation of downregulation can be examined through Meyer-Lindenberg's findings concerning the relationship between the MAOA-L allele and gray matter in the cingulate gyrus (Meyer-Lindenberg et al., 2006).
Using an MRI, Meyer-Lindenberg et al. (2006) examined the brains of healthy volunteers who either carried an MAOA-L or MAOA-H variant. The results showed that MAOA-L individuals showed significantly less gray matter in the cingulate gyrus relative to MAOA-H individuals, which indicates a weaker density of synaptic connections within this area (Meyer-Lindenberg et al., 2006). Notably, this area of the brain contains a high density of serotonin receptors. Thus, the findings suggest that serotonergic receptors may have shut down as a result of an accumulation of the monoamine neurotransmitter due to low enzymatic degradative activity (U.S. National Library of Medicine, 2020). However, downregulation cannot explain this phenomenon with absolute certainty, and more research is needed to corroborate this finding.
Interestingly, other studies have shown strong gene-environment interactions between the MAOA-L allele and the severity of childhood maltreatment. The most prominent study in this area was conducted by Caspi et al. Through a longitudinal study, 1307 participants from the Dunedin Multidisciplinary Health and Development Study—which has since published over 1300 works regarding health and behavioral development—were investigated every two years from the ages of three to twenty-one. Participants had varying levels of exposure to maltreatment during childhood, ranging from none, to moderate, to severe. To determine the levels of one’s aggressive behavior, participants periodically received diagnostic checks for personality disorders—such as aggressive personality disorder and conduct disorder. Participants were also assessed for behavioral issues and their conviction records were tracked periodically.
The results demonstrated that those with the MAOA-L variant who were maltreated as children were more likely to develop aggressive tendencies relative to those with the MAOA-H variant who experienced maltreatment at the same level. Additionally, those with the MAOA-L allele who were severely maltreated as children were far more likely to have a disposition towards violence compared to those who had the same variant and faced only probable maltreatment. These findings suggest that the combination of the MAOA-L allele and childhood maltreatment is particularly impactful in aggressive behavioral development.
Overall, it appears that monoamine oxidase A can elevate one’s sensitivity to aggressive behaviors to some extent, with this effect being most prominent in individuals with negative environmental experiences, such as childhood maltreatment. These findings have profound implications for understanding how the field can create intervention and prevention programs to minimize the prevalence of violence, especially among vulnerable populations.
About the Author
Sevillana Ettinger is a freshman at Boston University studying Psychology.
Brunner et al. (1993) was one of the first to discover a genetic basis for violent, aggressive behaviors. Based on a case study of a Dutch family with a vast history of violent males, he found an irregularity in the monoamine oxidase A (MAOA) gene, located in the X chromosome. Additionally, analysis of 24-hour urine samples indicated a deficiency in monoamine metabolism, which suggested a lack of degradation of monoamine neurotransmitters. Collectively, Brunner et al. realized the MAOA gene was not only potentially associated with the abnormal behavior of these males but was an indirect mediator of them; the gene seemed to be far more complex in its ability to dysregulate neurochemicals.
Currently, scientists now know that the MAOA gene produces the monoamine oxidase A enzyme, which is primarily responsible for the active degradation of monoamine neurotransmitters, such as serotonin (5-HT), to help prevent neurotransmitter accumulation within the brain (U.S. National Library of Medicine, 2020). Specifically, after the presynaptic cleft releases neurotransmitters to bind to receptors in the postsynaptic cleft, known as the target cell, the neurotransmitters are typically removed actively, such as through enzymatic degradation. This involves catabolizing the neurotransmitter within the synapse until it is no longer recognized by the receptors of the target cell (Jensen).
However, the MAOA-L allele produces a low-activity version of this enzyme, meaning serotonin will not be properly degraded. This results in an accumulation of this neurotransmitter in the brain, which appears to be a contributory factor to aggression. (U.S. National Library of Medicine, 2020).
The same effects between the MAOA-L allele, serotonergic accumulation, and aggressive behavior can be observed in mice, as demonstrated by Cases et al. (1995). The study compared aggression and impulsivity in Tg8 mice that had a deletion in MAOA exons 2 and 3, which developed the MAOA-L allele, while C3H mice had no MAOA deficiencies. One of their investigations involved a resident-intruder test, in which each mouse was placed in their typical cage with a two-month-old intruding mouse for ten minutes. The C3H mice appeared to investigate the cage, while Tg8 mice showed a “static, hunched, fluffed-fur posture” (p. 1764). Additionally, when the intruder was found, the Tg8 mice attacked the intruder faster than the C3H mice, suggesting impulsive, aggressive behavior. When later comparing the amount of serotonin in Tg8 and C3H brains, Cases et al. (1995) found that Tg8 mice showed extreme increases in serotonin compared to the C3H mice.
Interestingly, evidence of the effect of the MAOA-L allele in aggressive behavior can even be seen through brain activity and brain plasticity. Meyer-Lindenberg et al. (2006), for instance, conducted a study whereby MAOA-L and MAOA-H predisposed participants were exposed to images of neutral, fearful, and angry facial expressions under an fMRI. The results showed that when MAOA-L individuals viewed angry and fearful faces, they showed significant activation in the amygdala compared to individuals with the MAOA-H allele—one that predisposes high activity MAOA enzymes—viewed said facial expressions. Since the amygdala is a part of the brain associated with emotional response and impulsive reactivity, a high activation from this part of the brain suggests that threatening stimuli results in more impulsive, aggressive reactions in those with MAOA-L (Amaral, 2003). Thus, the correlation between the MAOA-L allele and the amygdala suggests the role of MAOA in aggressive behavior.
That said, there appears to be a perplexing relationship between the accumulation of serotonin and aggressive behavior. Serotonin is a neurotransmitter typically associated with prosocial behavior (Seigal & Crockett, 2013). Thus, intuitively, more serotonin in the brain would likely produce more prosocial effects. However, this contradiction was resolved by another brain analysis by Meyer-Lindenberg et al., which demonstrates the concept of down-regulation as the potential explanation. Downregulation is the process by which postsynaptic receptors shut off to prevent over-stimulating the brain with a particular neurotransmitter (U.S. National Library of Medicine, 2020). This aims to prevent excessive amounts of neurotransmitter from being transmitted throughout the brain. Further support for the explanation of downregulation can be examined through Meyer-Lindenberg's findings concerning the relationship between the MAOA-L allele and gray matter in the cingulate gyrus (Meyer-Lindenberg et al., 2006).
Using an MRI, Meyer-Lindenberg et al. (2006) examined the brains of healthy volunteers who either carried an MAOA-L or MAOA-H variant. The results showed that MAOA-L individuals showed significantly less gray matter in the cingulate gyrus relative to MAOA-H individuals, which indicates a weaker density of synaptic connections within this area (Meyer-Lindenberg et al., 2006). Notably, this area of the brain contains a high density of serotonin receptors. Thus, the findings suggest that serotonergic receptors may have shut down as a result of an accumulation of the monoamine neurotransmitter due to low enzymatic degradative activity (U.S. National Library of Medicine, 2020). However, downregulation cannot explain this phenomenon with absolute certainty, and more research is needed to corroborate this finding.
Interestingly, other studies have shown strong gene-environment interactions between the MAOA-L allele and the severity of childhood maltreatment. The most prominent study in this area was conducted by Caspi et al. Through a longitudinal study, 1307 participants from the Dunedin Multidisciplinary Health and Development Study—which has since published over 1300 works regarding health and behavioral development—were investigated every two years from the ages of three to twenty-one. Participants had varying levels of exposure to maltreatment during childhood, ranging from none, to moderate, to severe. To determine the levels of one’s aggressive behavior, participants periodically received diagnostic checks for personality disorders—such as aggressive personality disorder and conduct disorder. Participants were also assessed for behavioral issues and their conviction records were tracked periodically.
The results demonstrated that those with the MAOA-L variant who were maltreated as children were more likely to develop aggressive tendencies relative to those with the MAOA-H variant who experienced maltreatment at the same level. Additionally, those with the MAOA-L allele who were severely maltreated as children were far more likely to have a disposition towards violence compared to those who had the same variant and faced only probable maltreatment. These findings suggest that the combination of the MAOA-L allele and childhood maltreatment is particularly impactful in aggressive behavioral development.
Overall, it appears that monoamine oxidase A can elevate one’s sensitivity to aggressive behaviors to some extent, with this effect being most prominent in individuals with negative environmental experiences, such as childhood maltreatment. These findings have profound implications for understanding how the field can create intervention and prevention programs to minimize the prevalence of violence, especially among vulnerable populations.
About the Author
Sevillana Ettinger is a freshman at Boston University studying Psychology.
